scholarly journals Experimental validation and computational modeling of anti-influenza effects of quercetin-3-O-α-L-rhamnopyranoside from indigenous south African medicinal plant Rapanea melanophloeos

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Parvaneh Mehrbod ◽  
Samad Nejad Ebrahimi ◽  
Fatemeh Fotouhi ◽  
Fatemeh Eskandari ◽  
Jacobus N. Eloff ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Caspase 3 ◽  
Influenza Infection ◽  
Physical Interaction ◽  
Pandemic H1n1 ◽  
Binding Ability ◽  
Apoptosis Pathway ◽  
Protein Levels ◽  
Immunomodulatory Properties ◽  
Rapanea Melanophloeos

Abstract Background Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking. Methods MDCK cells were exposed to Q3R and 100CCID50/100 μl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R. Results The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of − 10.81, − 10.47, − 9.52, − 9.24 and − 8.78 Kcal/mol, respectively. Conclusions Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.

scholarly journals α -Lipoic Acid-Plus Ameliorates Endothelial Injury via Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in Vivo and Vitro Endothelial Injury Model

2021 ◽  
Author(s):  
Yang Wang ◽  
Xiangqian Kong ◽  
Dejun Bao ◽  
Bin xu ◽  
Yongfei Dong ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Caspase 3 ◽  
Endothelial Injury ◽  
Protective Effects ◽  
Apoptosis Pathway ◽  
Protein Levels ◽  
Oxidative Stress Level ◽  
Intimal Injury

Abstract PurposeWe tried to explore the potential role of the α-Lipoic acid-plus (LAP) in endothelial injury in vitro and vivo models. Simultaneously, possible endovascular protective mechanisms of LAP were also investigated further. MethodsIn vitro, oxyhemoglobin (OxyHb) stimulating human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, carotid artery angioplasty injury was used to generate a model of rat carotid artery intimal injury (CAII). HUVECs and rats were treated with desferrioxamine (DFO) and LAP. ResultsIn experiment 1, we found that the expressions of Cathepsin B/D in endothelial tissue increased and reached peak point in 48 hours post rat CAII. In experiment 2, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin, Transferrin Receptor (TfR) markedly increased after CAII and reversed by DFO and LAP treatments. Besides, DFO and LAP treatments also reduced oxidative stress level and endothelial cells (ECs) necrosis of the damaged endometrium. In experiment 3, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin and TfR apparently increased post OxyHb stimulation, which were further aggravated by the addition of iron and decreased by DFO and LAP treatments. Moreover, DFO and LAP significantly ameliorated oxidative stress level, HUVECs injury, iron level, mitochondrial damage and were beneficial to maintain lysosomal integrity. Finally, LAP may have exerted more significant endovascular protective effects than DFO.ConclusionsLAP probably exerted endovascular protective effects via inhibiting the apoptosis pathway mediated by intralysosomal Cathepsins by chelating excessive iron in endothelial lysosomes post intimal injury.

scholarly journals (Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose

2015 ◽  
Vol 309 (3) ◽  
pp. E302-E310 ◽  
Author(s):  
Caixia Li ◽  
Helmy M. Siragy
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Autophagic Flux ◽  
Bafilomycin A1 ◽  
Mtor Signaling Pathway ◽  
Autophagosome Formation ◽  
Podocyte Injury ◽  
Protein Levels

High glucose reduces autophagy and enhances apoptosis of podocytes. Previously, we reported that high glucose induced podocyte injury through upregulation of the (pro)renin receptor (PRR). We hypothesized that increasing PRR reduces autophagy and increases apoptosis of mouse podocytes exposed to high glucose via activation of the PI3K/Akt/mTOR signaling pathway. Mouse podocytes were cultured in normal (5 mmol/l) or high (25 mmol/l) d-glucose for 48 h. High glucose significantly increased mRNA and protein levels of PRR, phosphorylation of PI3K/Akt/mTOR, and p62. In contrast, high glucose decreased activation of UNC-51-like kinase-1 (ULK1) by phosphorylating Ser757 and protein levels of microtubule-associated protein-1 light chain 3B (LC3B)-II and Lamp-2. Bafilomycin A1 increased LC3BII and p62 accumulation in high-glucose-treated cells. High glucose reduced the autophagic flux. Confocal microscopy studies showed significant reduction in the protein level of LC3B in response to high glucose. Cyto-ID autophagy staining showed a significant decrease in autophagosome formation with high glucose. In the absence of PRR, activation of Akt with sc-79 or mTOR with MHY-1485 increased p62 accumulation. Caspase-3/7 activity and apoptosis monitored by TUNEL assay were significantly increased in podocytes treated with high glucose. PRR siRNA significantly reversed the effects of high glucose. Based on these data, we conclude that high glucose decreases autophagy and increases apoptosis in mouse podocytes through the PRR/PI3K/Akt/mTOR signaling pathway.

scholarly journals Immunization with 1976 swine H1N1- or 2009 pandemic H1N1-inactivated vaccines protects mice from a lethal 1918 influenza infection

2011 ◽  
Vol 5 (3) ◽  
pp. 198-205 ◽  
Author(s):  
Judith D. Easterbrook ◽  
John C. Kash ◽  
Zong-Mei Sheng ◽  
Li Qi ◽  
Jin Gao ◽  
...  
Keyword(s):  
Influenza Infection ◽  
Pandemic H1n1 ◽  
Inactivated Vaccines ◽  
1918 Influenza

Protective Effects of Crataegus pinnatifida Extracts and Crataegolic Acid Against Neurotoxicity of Paraquat in PC12 Cells

2021 ◽  
Vol 20 (1) ◽  
pp. 76-83
Author(s):  
Chi-Sen Chang ◽  
Yuh-Chiang Shen ◽  
Chi-Wen Juan ◽  
Chia-Lin Chang ◽  
Po-Kai Lin
Keyword(s):  
Reactive Oxygen Species ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Active Component ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
B Cell Lymphoma ◽  
Oxygen Species ◽  
Protein Levels ◽  
Crataegus Pinnatifida

The neuroprotective mechanisms of Crataegus pinnatifida extracts and crataegolic acid were studied using paraquat induced cytotoxicity in PC12 cells. C. pinnatifida extracts were prepared using hexane, ethyl acetate, and 95% ethanol. Additionally, crataegolic acid (also known as maslinic acid) was found in C. pinnatifida extracts. Assessment methods included the examinations of cytotoxicity, intracellular reactive oxygen species and calcium changes, activity of caspase-3 and α-synuclein, apoptotic cell death, and the expression levels of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins to investigate the neuroprotective mechanisms of C. pinnatifida extracts and its active component, crataegolic acid. The three extracts and crataegolic acid exhibited potent neuroprotective actions against paraquat induced PC12 cell apoptosis at 5–20µg/mL and 80–100µM concentrations, respectively. The key protective mechanisms included decreasing cell apoptosis, upregulating Bcl-2 protein levels, and downregulating Bax protein levels. The 95% ethanol extract also decreased paraquat induced reactive oxygen species production, calcium overloading, and caspase-3 and α-synuclein activities. The beneficial effects of these extracts could be explained by the active component, crataegolic acid that also inhibited paraquat-induced apoptosis through the suppression of reactive oxygen species generation and the caspase-3 signaling pathway.

scholarly journals Overexpression of IRS-4 Correlates with Procaspase 3 Levels in Tumoural Tissue of Patients with Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Patricia Sanmartín-Salinas ◽  
Luis G. Guijarro
Keyword(s):  
Colorectal Cancer ◽  
Caspase 3 ◽  
Cultured Cells ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation ◽  
Tnm System ◽  
Protein Levels ◽  
Receptor Signalling ◽  
T Values

We reported that insulin receptor substrate 4 (IRS-4) levels increased in tissue from colorectal cancer (CRC) patients and promoted retinoblastoma-cyclin-dependent kinase activation. The aim of the present study was to evaluate the effect of IRS-4 on IGF-1 receptor pathway and its impact on procaspase 3 and PARP expression in RKO and HepG2 cancer cell lines. The results obtained in vitro were compared with those obtained from biopsies of patients with CRC (n = 18), tubulovillous adenomas (TA) (n = 2) and in matched adjacent normal colorectal (MANC) tissue (n = 20). IRS-4 overexpression in cultured cells induced the overactivation of IGF-1/BRK/AKT/GSK-3/β-catenin/cyclin D1 pathways, which led to increased expression of procaspase 3 and PARP protein levels. Studies carried out on CRC and TA tissues revealed the overactivation of the IGF-1 receptor signalling pathway, as well as the overexpression of procaspase 3 and PARP in tumoural tissue with respect to MANC tissue. The upregulation of IRS-4 in tumoural samples correlated significantly with the increase in pIGF-1 receptor (Tyr 1165/1166) (r = 0.84; p < 0.0001), procaspase 3 (r = 0. 77; p < 0. 0005) and PARP (r = 0. 89; p < 0. 0005). Similarly, we observed an increase in the proteolysis of procaspase 3 in tumoural tissue with respect to MANC tissue, which correlated significantly with the degradation of PARP (r = 0.86; p < 0.0001), p53 (r = 0.84; p < 0.0001), and GSK-3 (r = 0.78; p < 0.0001). The stratification of patient samples using the TNM system revealed that procaspase 3 and caspase 3 increased gradually with T values, which suggests their involvement in the size and local invasion of primary tumours. Taken together, our findings suggest that IRS-4 overexpression promotes the activation of the IGF-1 receptor pathway, which leads to the increase in procaspase 3 levels in CRC.

scholarly journals Modulatory effect of Persea Americana oil against diethylnitrosamine-induced hepatotoxicity in rats: a proposed mechanism

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Omayma A. R. Abozaid ◽  
Lobna M. Anees ◽  
Gehan R. Abdel-Hamed
Keyword(s):  
Nadph Oxidase ◽  
Caspase 3 ◽  
Persea Americana ◽  
Gene Expressions ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Apoptotic Effect ◽  
Oxide Synthase ◽  
Parp 1 ◽  
Inducible Nitric Oxide

Abstract Background The purpose of this study was to investigate the effectiveness of Persea Americana (avocado) oil against diethylnitrosamine (DEN)-induced hepatotoxicity in rats. Methods For the induction of hepatotoxicity, DEN was administrated orally in a dose of 20 mg/kg B.wt for 6 successive weeks, and then the animals were gavaged with Persea Americana oil in a dose of 4 mL/kg b.wt. daily for another 6 weeks. Serum caspase-3 activity and poly (ADP-ribose) polymerase-1 (PARP-1) levels were estimated; in addition to gene expressions for NADPH oxidase, inducible nitric oxide synthase (iNOS), Bcl-2, and Bax were detected. Results The DEN-intoxicated group exhibited a remarkable increase in NADPH oxidase and iNOS expression combined with over-activation of PARP-1 and increased antiapoptotic Bcl-2 gene expression, whereas the expression of apoptotic biomarkers significantly decreased. On the other hand, treatment with Persea Americana oil significantly suppressed the elevated levels of hepatic enzymes and improved histopathological alterations in the liver. Furthermore, these groups displayed marked downregulation in NADPH oxidase and iNOS expressions. Persea Americana oil suppressed the expression of the antiapoptotic Bcl-2, activated the intrinsic mitochondrial apoptosis pathway through upregulation of pro-apoptotic Bax, and induced an obvious increase in caspase-3 activity. Moreover, Persea Americana oil administration markedly inhibited the activity of PARP-1. Conclusions This study indicated the promising potential of Persea Americana oil against DEN-induced hepatic injury through its anti-oxidative activity and pro-apoptotic effect via caspase activation and PARP-1 inhibition.

scholarly journals Expression levels of caspase-3 and gasdermin E and their involvement in the occurrence and prognosis of lung cancer

2021 ◽  
Author(s):  
yuanli huang ◽  
GuangHui Zhang ◽  
Qing Zhu ◽  
Xia Wu ◽  
LIGao Wu
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Clinical Stage ◽  
The Body ◽  
Caspase 8 ◽  
Survival Prognosis ◽  
Expression Levels ◽  
Protein Levels ◽  
Normal Tissues ◽  
Related Proteins

Abstract Background Pyroptosis plays a dual role in the development of cancer and malignancy, and as such, may potentially be a new target for cancer treatment. However, the inflammatory response to pyroptosis may have adverse effects on the body. The roles of gasdermin E (GSDME), caspases, and related proteins associated with pyroptosis in cancer remain controversial. This study aimed to explore whether the expression levels of caspase-3 and GSDME affect the clinical stage, pathological grade, and survival prognosis of patients with lung cancer. Methods We examined the protein levels of GSDME, caspase-3, caspase-8, and caspase-9 in lung tissues from 100 patients with lung cancer by using immunohistochemistry. Results We found that GSDME, caspase-3, and caspase-8 were more highly expressed in the tumor tissues than in the adjacent normal tissues. Moreover, we found that GSDME could serve as a prognostic factor because there was a positive correlation between its expression level and the postoperative survival rate of patients with lung cancer. Conclusions GSDME may be an independent factor affecting the prognosis of patients with lung cancer. However, the role of GSDME and its related proteins in cancer requires further research.

scholarly journals Decreased ZO1 expression causes loss of time-dependent tight junction function in the liver of ob/ob mice

2021 ◽  
Author(s):  
Yuya Tsurudome ◽  
Nao Morita ◽  
Michiko Horiguchi ◽  
Kentaro Ushijima
Keyword(s):  
Tight Junction ◽  
Dark Period ◽  
Vital Role ◽  
Time Dependent ◽  
Signal Transduction System ◽  
Binding Ability ◽  
Protein Levels ◽  
Multiple Organs ◽  
Zonula Occludens ◽  
Zonula Occludens 1

Abstract Diabetes patients are at a high risk of developing complications related to angiopathy and disruption of the signal transduction system. The liver is one of the multiple organs damaged during diabetes. Few studies have evaluated the morphological effects of adhesion factors in diabetic liver. The influence of diurnal variation has been observed in the expression and functioning of adhesion molecules to maintain tissue homeostasis associated with nutrient uptake. The present study demonstrated that the rhythm-influenced functioning of tight junction was impaired in the liver of ob/ob mice. The tight junctions of hepatocytes were loosened during the dark period in normal mice compared to those in ob/ob mice, where the hepatocyte gaps remained open throughout the day. The time-dependent expression of zonula occludens 1 (ZO1) in the liver plays a vital role in the functioning of the tight junction. The time-dependent expression of ZO1 was nullified and its expression was attenuated in the liver of ob/ob mice. ZO1 expression was inhibited at the mRNA and protein levels. The expression rhythm of ZO1 was found to be regulated by heat shock factor (HSF)1/2, the expression of which was reduced in the liver of ob/ob mice. The DNA-binding ability of HSF1/2 was decreased in the liver of ob/ob mice compared to that in normal mice. These findings suggest the involvement of impaired expression and functioning of adhesion factors in diabetic liver complications.

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